title: Hydroxydibenzoylmethane induces apoptosis through repressing ornithine decarboxylase in human promyelocytic leukemia HL-60 cells.
abstract: Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis and a target for chemoprevention. Hydroxydibenzoylmethane (HDB), a derivative of dibenzoylmethane of licorice, is a promising chemopreventive agent. In this paper, we investigated whether HDB would inhibit the ODC pathway to enhance apoptosis in human promyelocytic leukemia HL-60 cells. We found ODC enzyme activity was reduced during HDB treatment. Overexpression of ODC in HL-60 parental cells could reduce HDB-induced apoptosis, which leads to loss of mitochondrial membrane potential (Δψ(m)), through lessening intracellular ROS. Furthermore, ODC overexpression protected cytochrome c release and the activation of caspase-3 following HDB treatment. The results demonstrated HDB-induced apoptosis was through a mechanism of down-regulation of ODC and occurred along a ROS-dependent mitochondria-mediated pathway.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Ming-Fu
authors.initials: MF
authors.lastname: Wang
authors.forename: Ya-Fan
authors.initials: YF
authors.lastname: Liao
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Hung
authors.forename: Chih-Li
authors.initials: CL
authors.lastname: Lin
authors.forename: Tzyh-Chyuan
authors.initials: TC
authors.lastname: Hour
authors.forename: Ko-Huang
authors.initials: KH
authors.lastname: Lue
authors.forename: Hui-Chih
authors.initials: HC
authors.lastname: Hung
authors.forename: Guang-Yaw
authors.initials: GY
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D047188:Chalcones / Q000378:metabolism / Q000494:pharmacology*; D018890:Chemoprevention; D045304:Cytochromes c / Q000096:biosynthesis / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D018922:HL-60 Cells; D006801:Humans; D015151:Immunoblotting; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D047188:Chalcones; D065108:Ornithine Decarboxylase Inhibitors; D017382:Reactive Oxygen Species; C476492:hydroxydibenzoylmethane; D045304:Cytochromes c; D053148:Caspase 3; D009955:Ornithine Decarboxylase